1. Prevalence, Predictors, and Long-Term Prognosis of Premature Discontinuation of Oral Antiplatelet Therapy After Drug Eluting Stent Implantation Roberta Rossini, MD, PhD, Davide Capodanno, MD, Corrado Lettieri, MD, Giuseppe Musumeci, MD, Tamar Nijaradze, MD, Michele Romano, MD, Nikoloz Lortkipanidze, MD, Nicola Cicorella, MD, Giuseppe Biondi Zoccai, MD, Vasile Sirbu, MD, Antonio Izzo, MD, Giulio Guagliumi, MD, Orazio Valsecchi, MD, Antonello Gavazzi, MD and Dominick J. Angiolillo, MD, PhD USC Cardiologia, Dipartimento Cardiovascolare, Ospedali Riuniti di Bergamo, Italy Divisione di Cardiologia, Ospedale Carlo Poma, Mantova, Italy Divisione di Cardiologia, Università di Torino, Italy University of Florida College of Medicine- Jacksonville, Florida, US American Journal of Cardiology Volume 107, Issue 2, Pages 186-194Volume 107, Issue 2, Pages 186-194 (January 2011) DOI: 10.1016/j.amjcard.2010.08.067 Copyright © 2011 Elsevier Inc. Terms and ConditionsTerms and Conditions

2. Aim of the Study The aims of the present study were to determine the prevalence and predictors of premature discontinuation of long-term oral antiplatelet therapy after DES implantation and to evaluate its effects on prognosis in relation to the time and duration of the discontinuation

3. Methods We studied 1358 consecutive pts treated with DES and discharged on dual antiplatelet therapy with aspirin (100 mg/day) and clopidogrel (75 mg/day) Clopidogrel was maintained for 12 months Pts were followed-up for 32.4±11.3 months Prevalence and predictors of aspirin and/or clopidogrel discontinuation were assessed Major adverse cardiac events (MACE), defined as death, acute coronary syndrome leading to hospitalization, and stroke, were recorded. Probable/possible/definite stent thrombosis were also recorded

4. Rossini R et al. Am J Card 2011, 107: 186-194 Discontinuation Causes: Surgery 34.5% Bleeding 21% Medical decision 17.6% Dental interventions 7.6% Economic/burocratic reasons 5.9% Anticoagulant therapy 5.0% Results 8.8% of patients discontinued one or both antiplatelet agents within the first 12 months (early discontinuation) and 4.8% withdrew aspirin after 1 year (late discontinuation)

5. Predictors of Discontinuation Early Discontinuation in-hospital major bleeding (OR=9.00, p<0.001) statins at discharge (OR=0.36, p<0.001) oral anticoagulants at discharge (OR=8.21, p<0.001) Late Discontinuation history of prior stroke (OR=5.21, p<0.001) Rossini R et al. Am J Card 2011, 107: 186-194

6. Patients who discontinued antiplatelet therapy had a higher incidence of death, MACE and stent thrombosis MACE % Discontinuation and Prognosis Rossini R et al. Am J Card 2011, 107: 186-194

7. Overall death and discontinuation 100 90 80 70 60 50 40 48 3624 12 Survival (%) Months Log rank test Overall: p=0.001 No discontinuation vs early discontinuation: p=0.001 No discontinuation vs late discontinuation: p=0.223 Early discontinuation vs late discontinuation: p=0.011 No discontinuation vs early+late discontinuation: p=0.018 Late discontinuation Early discontinuation No discontinuation Rossini R et al. Am J Card 2011, 107: 186-194

8. 100 90 80 70 60 50 40 48 36 24 12 Survival free from MACE (%) Log rank test Overall: p=0.001 No discontinuation vs early discontinuation: p=0.001 No discontinuation vs late discontinuation: p=0.223 Early discontinuation vs late discontinuation: p=0.011 No discontinuation vs early+late discontinuation: p=0.018 Late discontinuation Early discontinuation No discontinuation MACE and discontinuation Months Rossini R et al. Am J Card 2011, 107: 186-194

9. Survival free from Stent Thrombosis (%) 100 90 80 70 60 50 40 48 36 24 12 0 0 Log rank test Overall: p=0.031 No discontinuation vs early discontinuation: p=0.015 No discontinuation vs late discontinuation: p=0.175 Early discontinuation vs late discontinuation: p=0.653 No discontinuation vs early+late discontinuation: p=0.009 Months Late discontinuation Early discontinuation No discontinuation Stent Thrombosis and discontinuation Rossini R et al. Am J Card 2011, 107: 186-194

10. Death, MACE or stent thrombosis and time of discontinuation % P=0.10 P=0.02 P=0.008 P for trend = 0.004 P=0.10 P=0.02 P=0.008 P for trend = 0.004 P=0.10 P=0.02 P=0.008 P for trend = 0.004 Rossini R et al. Am J Card 2011, 107: 186-194

11. Association between thienopyridine and/or aspirin discontinuation and MACE stratified by time intervals Discuntinuation of Both Discuntinuation of Thienopyridines Only Discuntinuation of Aspirin Only No Discontinuation P=1.0 P=0.88 P = 0.20 P=0.26 P=0.001 P = 0.24P=0.08 P=0.002 P=0.001 P=1.00 P=0.11 P = 0.07 % Rossini R et al. Am J Card 2011, 107: 186-194

12. Conclusions Premature discontinuation of antiplatelet therapy is relatively common, especially within the first year, and strongly associated with increased cardiovascular events, including ST and death. Early discontinuation of antiplatelet agents within the first year was predicted by in-hospital major bleeding, oral anticoagulant use at discharge, and the lack of statin prescription. Strategies to improve compliance to antiplatelet therapy in patients with greater likelihood to interrupt treatment are warranted